A 2A adenosine receptor agonists, antagonists, inverse agonists and partial agonists.

The Gs-coupled A _2A adenosine receptor (A _2A AR) has been explored extensively as a pharmaceutical target, which has led to numerous clinical trials. However, only one selective A _2A AR agonist (regadenoson, Lexiscan) and one selective A _2A AR antagonist (istradefylline, Nouriast) have been approved by the FDA, as a pharmacological agent for myocardial perfusion imaging (MPI) and as a cotherapy for Parkinson's disease (PD), respectively. Adenosine is widely used in MPI, as Adenoscan. Despite numerous unsuccessful clinical trials, medicinal chemical activity around A _2A AR ligands has accelerated recently, particularly through structure-based drug design. New drug-like A _2A AR antagonists for PD and cancer immunotherapy have been identified, and many clinical trials have ensued. For example, imaradenant (AZD4635), a compound that was designed computationally, based on A _2A AR X-ray structures and biophysical mapping. Mixed A _2A AR/A _2B AR antagonists are also hopeful for cancer treatment. A _2A AR antagonists may also have potential as neuroprotective agents for treatment of Alzheimer's disease.
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